Pharmaceutical salts

ABSTRACT

The invention relates to pharmaceutical salts comprised of a pharmaceutical active substance and of a least one sugar substitute, to medicaments containing these salts, and to the use of these salts for producing medicaments.

The present invention relates to pharmaceutical salts of an activecompound and at least one sugar substitute, medicaments comprising thesesalts, and the use of these salts for the production of medicaments.

On oral administration, a large number of pharmaceutical activecompounds having excellent activity lead to a strongly bitter, oftennauseating taste sensation in the patient. In some patients, lack ofadherence to the dosage instructions and a lack of acceptance of thecorresponding medicaments which release such an active compound as earlyas during taking result from this negative taste experience.

The formulation of pharmaceutical active compounds having very goodwater solubility to give medicaments frequently causes problems inpharmaceutical practice. Thus the preparation of pharmaceutical formshaving controlled release is often made difficult on account of the verygood water solubility of active compound salts. A delaying of therelease of these active compounds can in fact be achieved, for example,by coating the pharmaceutical forms with release-delaying film coatings.This manner of delaying the release, however, is associated with arelatively high outlay, since release-delaying film coatings fromaqueous coating systems are frequently only an inadequate diffusionbarrier for active compounds having very good water solubility. Thepreparation of these delayed-release active compound preparationstherefore requires relatively complicated coating processes withmultilayer films. If such release-delaying coatings are applied fromorganic solvents, the environmental and solvent residue problemsassociated therewith additionally make the preparation of appropriatepreparations more expensive.

It was therefore the object of the present invention to make availablepharmaceutical combinations of active compounds which have no bittertaste. Preferably, the corresponding active compounds should be simplerto formulate and their release should be more effectively delayed.

According to the invention, this object is achieved by the provision ofpharmaceutical salts, i.e. physiologically tolerable salts, from apharmaceutical active compound and at least one sugar substitute.

The present invention therefore relates to pharmaceutical salts of apharmaceutical active compound and at least one sugar substitute, therespective pharmaceutical salts of a sugar substitute and tramadol,(+)-tramadol, (−)-tramadol, (+)-demethyltramadol and(−)-demethyltramadol being excepted.

In a preferred embodiment of the present invention, the solubility ofthe pharmaceutical salts according to the invention in water is ≦250mg/ml of water, preferably ≦200 mg/ml, particularly preferably ≦150mg/ml, very particularly preferably ≦100 mg/ml. This can also be seen inparticular in the fact that the water solubility of the pharmaceuticalsalts according to the invention compared with the water solubility ofthe best water-soluble salt of the corresponding active compoundaccording to Pharmazeutische Stoffliste [Pharmaceutical Substance List],12th edition ABDATA Pharma-Daten-Service, 65735 Eschborn/Taunus, ispreferably lowered by at least 50%, preferably by at least 65%,particularly preferably by at least 75%, very particularly preferably byat least 85%, compared with the corresponding hydrochloride. Thecorresponding literature description is hereby inserted as a referenceand is thus regarded as part of the disclosure.

According to the invention, suitable sugar substitutes are all sugarsubstitutes which can form a salt with the respective pharmaceuticalactive compound with formation of an at least singly negatively chargedform. According to the invention, pharmaceutical salts are also includedin which the pharmaceutical active compound has two or more differentsugar substitutes as salt components. Preferably, the pharmaceuticalsalts according to the invention contain saccharin, cyclamate oracesulfam, particularly preferably saccharin, as salt-forming sugarsubstitutes.

According to the invention, suitable active compounds are allpharmaceutical active compounds which can form a salt in anionic formwith the respective sugar substitute(s) with formation of an at leastsingly positively charged form.

In a further preferred embodiment of the present invention, thesalt-forming active compound in the pharmaceutical salt according to theinvention is selected from the group consisting of the salt-forminganalgesics, antiobesity agents, analeptics, antihypoxemics,antirheumatics, opioid antagonists, anthelmintics, antiallergics,antiarrhythmics, antibiotics, antidementives (nootropics),antidiabetics, antiemetics, antivertiginous agents, antiepileptics,antihypertensives, antihypotensives, antimycotics, antiinflammatories,antitussives, expectorants, arteriosclerosis agents, P-receptorblockers, calcium channel blockers, broncholytics, antiasthmatics,cholinergics, diuretics, circulation-promoting agents, weaning agents,geriatrics, hypnotics, sedatives, immunomodulators, oral therapeutics,pharyngeal therapeutics, coronary agents, hypolipidemics, localanesthetics, neural therapeutics, gastric agents, intestinal agents,migraine agents, muscle relaxants, anesthetics, neuropathy preparations,ophthalmologicals, otologicals, Parkinson agents, psychopharmaceuticals,rhinologicals, sinusitis agents, spasmolytics, platelet aggregationinhibitors, tuberculosis agents, urologicals and cytostatics.Particularly preferably, the salt-forming active compound is selectedfrom the group consisting of the salt-forming analgesics, analeptics,antihypoxemics, antiallergics, antiarrhythmics, antiemetics,antivertiginous agents, antihypertensives, antihypotensives,antitussives, expectorants, β-receptor blockers, calcium channelblockers, ophthalmologicals, otologicals, spasmolytics and urologicals.Very particularly preferably, the salt-forming active compound isselected from the group consisting of the salt-forming analgesics,tramadol, (+)-tramadol, (−)-tramadol, (+)-demethyltramadol and(−)-demethyltramadol being excepted.

If the pharmaceutical active compound is a salt-forming analgesic, it ispreferably a salt-forming opioid or a salt-forming opioid analog, suchas disclosed in E. Friderichs, T. Christoph, H. Buschmann, “Analgesicsand Antipyretics”; Ullmann's Encyclopedia of Industrial Chemistry, SixthEdition on CD-ROM, Wiley-VCH, Weinheim, 2000 or in Pharmaceuticals, J.L. McGuire (Editor), Analgesics and Antipyretics, Volume 2, pages341-434, Wiley-VCH, Weinheim or ephedrine, chloroquine, lidocaine,ethaverine, preglumetacin or triflupromazine. The correspondingdisclosures are hereby inserted as a reference and are thus regarded aspart of the present disclosure. Particularly preferably, thesalt-forming analgesic is selected from the group consisting ofmorphine, codeine, ethylmorphine, diacetylmorphine, dihydrocodeine,etorphine, hydrocodone, hydromorphone, levorphanol, oxycodone,oxymorphone, pethidine, ketobemidone, fentanyl, alfentanil,remifentanil, sufentanil, levomethadone, levomethadyl, dextro-moramide,dextropropoxyphene, diphenoxylate, piri-tramide, tilidine,buprenorphine, butorphanol, dezozine, meptazinol, nalbuphine,nalorphine, pentazo-cine, flupirtin and nefopam or a representative ofthe group consisting of ephedrine, chloroquine, lidocaine, ethaverine,preglumetacin and triflupromazine. Very particularly preferably, thesalt-forming analgesic is a salt-forming opioid or opioid analogselected from the group consisting of morphine, codeine, hydrocodone,hydromorphone, oxycodone, tilidine, fentanyl and buprenorphine.

Likewise preferably, the salt-forming active compound is a salt-formingcompound of 1-phenyl-3-dimethylaminopropane compounds of the generalformula I

in which in each case

-   -   X is OH, F, Cl, H or an OCOR⁶ group,    -   R¹ is a C₁₋₄-alkyl group,    -   R² is H or a C₁₋₄-alkyl group and R³ is H or a straight-chain        C₁₋₄-alkyl group or the radicals R² and R³ together form a        C₄₋₇-cycloalkyl radical, and    -   if R⁵ is H, R⁴ is meta-O-Z where Z is H, C₁₋₃-alkyl,        PO(O—C₁₋₄-alkyl)₂, CO(OC₁₋₅-alkyl), CONH—C₆H₄—(C₁₋₃-alkyl),        CO—C₆H₄—R⁷, where R⁷ is ortho-OCOC₁₋₃-alkyl or meta- or        para-CH₂N(R⁸)₂ where R⁸ is C₁₋₄-alkyl or 4-morpholino, or R⁴ is        meta-S—C₁₋₃-alkyl, meta-Cl, meta-F, meta-CR⁹R¹⁰R¹¹ where R⁹, R¹⁰        and R¹¹ are H or F, ortho-OH, ortho-O—C₂₋₃-alkyl, para-F or        para-CR⁹R¹⁰R¹¹ where R⁹, R¹⁰, R¹¹ are H or F, or if R⁵ is        para-Cl, —F, —OH or —O—C₁₋₃-alkyl, R⁴ is meta-Cl, —F, —OH or        —O—C₁₋₃-alkyl, or    -   R⁴ and R⁵ together are 3,4-OCH═CH— or 3,4-OCH═CHO—,    -   R⁶ is C₁₋₃-alkyl,    -   in the form of their possible stereoisomers as racemates or        diastereomerically pure enantiomers or in the form of mixtures        of enantiomers, in which the respective enantiomers are present        in nonequimolar amounts.

Preferred is a salt-forming compound of 1-phenyl-3-dimethylaminopropanecompounds of the general formula I in which X is OH, F, Cl or H, R¹ is aC₁₋₄-alkyl group, R² is H or CH₃ and R³ is H or CH₃ and if R⁵ is H, R⁴is meta-O—C₁₋₃-alkyl, meta-OH, meta-S—C₁₋₃-alkyl, meta-F, meta-Cl,meta-CH₃, meta-CF₂H, meta-CF₃ or para-CF₃ or if R⁵ is a para-Cl or —F,R⁴ is meta-Cl or —F, or R⁴ and R⁵ together are 3,4-OCH═CH—.

Particularly preferred is a salt-forming compound of1-phenyl-3-dimethylaminopropane compounds of the general formula I inwhich the radicals R² and R³ have different meanings and which arepresent in the form of their diastereomers having the configuration Ia

Very particularly preferred is a salt-forming compound of1-phenyl-3-dimethylaminopropane compounds of the general formula I,selected from the group consisting of

-   -   (1RS,2RS)-3-(3-dimethylamino-1-hydroxy-1,2-dimethylpropyl)phenol,    -   (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol,    -   (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol,    -   (2RS,3RS)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol,    -   (−)-(1S,2S)-3-(3-dimethylamino-1-ethyl-1-fluoro-2-methylpropyl)phenol,    -   (+)-(1R,2R)-3-(3-dimethylamino-1-hydroxy-1,2-dimethylpropyl)phenol,    -   (+)-(2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol        and    -   (−)-(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol.

The preparation of the salt-forming compounds of1-phenyl-3-dimethylaminopropane compounds of the general formula I and,if appropriate, the separation into the pure optical antipodes can becarried out according to customary methods known to the person skilledin the art. Preferably, the preparation and, if appropriate, theseparation is carried out as described in DE-A-4426245 or EP 0 693 475B1, which are hereby inserted as reference and are thus regarded as partof the disclosure.

In a further preferred embodiment of the present invention, thepharmaceutical salt according to the invention contains as asalt-forming active compound a salt-forming compound of6-dimethylaminomethyl-1-phenylcyclohexane compounds of the generalformula II,

in which in each case

-   -   R^(1′) is H, OH, Cl or F, preferably H, OH or F,    -   R^(2′) and R^(3′) are identical or different and are H,        C₁₋₄-alkyl, benzyl, CF₃, OH, OCH₂—C₆H₅, O—C₁₋₄-alkyl, Cl or F        with the proviso that at least one of the radicals R^(2′) or        R^(3′) is H,    -   R^(4′) is H, CH₃, PO(O—C₁₋₄-alkyl)₂, CO(OC₁₋₅-alkyl),        CO—NH—C₆H₄—C₁₋₃-alkyl, CO—C₆H₄—R^(5′), CO—C₁₋₅-alkyl,        CO—CHR^(6′)—NHR^(7′) or an unsubstituted or substituted pyridyl,        thienyl, thiazoyl [sic] or phenyl group,    -   R^(5′)is OC(O)C₁₋₃-alkyl in the ortho-position or CH₂—N(R⁸′)₂ in        the meta- or para-position, where R^(8′) is C₁₋₄-alkyl or both        radicals R^(8′) together with N are the 4-morpholino radical,        and    -   R^(6′) and R^(7′) are identical or different and are H or        C₁₋₆-alkyl,    -   with the proviso that if both radicals R^(2′) and R^(3′) are H,        R^(4′) is not CH₃ if R^(1′) is H, OH or Cl or R^(4′) is not H if        R^(1′) is OH,    -   in the form of their possible stereoisomers as racemates or        diastereomerically pure enantiomers or in the form of mixtures        of enantiomers, in which the respective enantiomers are present        in nonequimolar amounts.

Preferred are salt-forming compounds of6-dimethylaminomethyl-1-phenylcyclohexane compounds of the generalformula II, which are present in the configuration as in the generalformula IIa,

in which the phenyl ring and the dimethylaminomethyl group are in eachcase arranged in an equatorial position to one another.

Particularly preferred is a salt-forming compound ofb-dimethylaminomethyl-1phenylcyclohexane compounds of the generalformula II selected from the group consisting of

-   -   (−)-(1R,2R)-3-(2-dimethylaminomethylcyclohexyl)phenol,    -   (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexane-1,3-diol        and    -   (1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3-hydroxyphenyl)cyclohexane-1,3-diol.

The preparation of the salt-forming compounds of6-dimethylaminomethyl-1-phenylcyclohexane compounds of the generalformula II and, if appropriate, the separation into the optically pureantipodes can be carried out according to customary methods known to theperson skilled in the art. Preferably, the preparation and, ifappropriate, the separation are carried out as described inDE-A-19525137. The corresponding literature description is herebyinserted as reference and is thus regarded as part of the disclosure.

In a further preferred embodiment of the present invention, thepharmaceutical salt according to the invention contains as asalt-forming active compound a salt-forming compound of1-phenyl-2-dimethylamino-methylcyclohexan-1-ol compounds of the generalformula III,

in which in each case

-   -   A is O or S,    -   R^(1″) is H, C₁₋₆-alkyl, C₂₋₆-alkenyl, C₅₋₇-cycloalkyl or        halogenated C₁₋₆-alkyl,    -   the group        is the group    -   R^(2″) is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₅₋₇-cycloalkylmethyl,        substituted or unsubstituted phenyl or substituted or        unsubstituted benzyl,    -   in the form of their possible stereoisomers as racemates or        diastereomerically pure enantiomers or in the form of mixtures        of enantiomers, in which the respective enantiomers are present        in nonequimolar amounts.

Preferred are salt-forming compounds of1-phenyl-2-di-methylaminomethylcyclohexan-1-ol compounds of the generalformula III, in which R^(1″) is H, C₁₋₄-alkyl, 2′-methyl-2′-propenyl,cyclopentyl or fluoroethyl, with the proviso that R^(1″) is C₁₋₄-alkylif A is S,

-   -   R^(2″) is C₁₋₄-alkyl, C₂₋₄-alkenyl, cyclopentylmethyl, phenyl,        C₁₋₄-alkoxyphenyl, benzyl, C₁₋₄-alkylbenzyl, mono- or        dihalogenated phenyl or mono- or dihalogenated benzyl.

Particularly preferred are salt-forming compounds of1-phenyl-2-dimethylaminomethylcyclohexan-1-ol compounds of the generalformula III, in which R^(1″) is H, methyl, ethyl, isopropyl,2′-methyl-2′-propenyl, cyclopentyl or fluoroethyl, with the proviso thatR^(1″) is methyl if A is S,

-   -   R^(2″) is methyl, propyl, 2′-methylpropyl, allyl,        2′-methyl-2′-propenyl, cyclopentylmethyl, phenyl,        3-methoxyphenyl, benzyl, 4-tert-butylbenzyl, 4-chloro-benzyl,        4-fluorobenzyl or 3,4-dichlorobenzyl.

Very particularly preferred are salt-forming compounds of1-phenyl-2-dimethylaminomethylcyclohexan-1-ol compounds of the generalformula III which are present in the configuration of the formula IIIa,

in which the phenyl ring and the dimethylaminomethyl group are in eachcase arranged in an equatorial position to one another.

Most preferred is the salt-forming compound of1-phenyl-2-dimethylaminomethylcyclohexan-1-ol compounds of the generalformula III selected from the group consisting of

-   -   (+)-(1R,2R,4S)-2-(dimethylaminomethyl)-4-(4-fluorobenzyloxy)-1-(3-methoxyphenyl)cyclohexanol,

1(+)-(1R,2R,4S)-2-dimethylaminomethyl-4-(4-chlorobenzyloxy)-1-(3-methoxyphenyl)cyclohexanoland

-   -   (+)-(1R,2R,4S)-3-[2-dimethylaminomethyl-4-(4-fluorobenzyloxy)-1-hydroxycyclohexyl]phenol.

The preparation of the salt-forming compounds of1-phenyl-2-dimethylaminomethylcyclohexan-1-ol compounds of the generalformula III and, if appropriate, the separation into the optically pureantipodes can be carried out according to customary methods known to theperson skilled in the art. Preferably, the preparation and, ifappropriate, the separation are carried out as described inDE-A-19547766, which is hereby inserted as reference and is thusregarded as part of the disclosure.

In a further preferred embodiment of the present invention, thepharmaceutical salt contains as a salt-forming active compound asalt-forming compound of dimethyl-(3-arylbut-3-enyl)amine compounds ofthe general formula IV, in which [sic]

the radical R^(1′″) is C₁₋₅-alkyl and R^(2′″) is H or C₁₋₅-alkyl orR^(1′″) and R^(2′″) together are —(CH₂)₂₋₄—, —(CH₂)₂—CHR^(7′″) or—CH₂—CHRR^(7′″)—CH₂—,

-   -   R^(3′″) is H or C₁₋₅-alkyl,    -   R^(4′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl, CF₃,        O—CF₃, Cl, F or OR^(′″),    -   R^(5′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl, CHF₂, CF₃,        O—CF₃, Cl, F or OR^(8′″) and    -   R^(6′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl, CF₃,        O—CF₃, Cl, F or OR^(8′″),    -   with the proviso that two of the radicals R^(4′″), R^(5′″) or        R^(6′″) are H, or    -   R^(4′″) and R^(5′″) together are —CH═C(R^(9′″))—O— or        —CH═C(R^(9′″))—S—, with the proviso that R^(6′″) is H, or    -   R^(5′″) and R^(6′″) together are —CH═CH—C(OR^(10′″))═CH—, with        the proviso that R^(4′″) is H,    -   R^(7′″) is C₁₋₈-alkyl, C₃₋₈-cycloalkyl, O—C₁₋₄-alkyl, O-benzyl,        CF₃, Cl or F.    -   R^(8′″) is CO—C₁₋₅-alkyl, PO(O—C₁₋₄-alkyl)₂, CO—C₆H₄—R^(11′″),        CO(O—C₁₋₅-alkyl), CO—CHR^(12′″)—NHR^(13′″),        CO—NH—C₆H₃—(R^(14′″))₂ or an unsubstituted or substituted        pyridyl, thienyl, thiazoyl [sic] or phenyl group,    -   R^(9′″) is H or C₁₋₄-alkyl,    -   R^(10′″) is H or C₁₋₃-alkyl,    -   R^(11′″) is OC(O)—C₁₋₃-alkyl in the ortho-position or        CH₂—N—(R^(15′″))₂ in the meta- or para-position, where R^(15′″)        is C₁₋₄-alkyl or both radicals R^(15′″) together with N form the        4-morpholino radical,    -   R^(12′″) and R^(13′″) are identical or different and are H,        C₁₋₆-alkyl or C₃₋₈-cycloalkyl or R^(12′″) and R^(13′″) together        are —(CH₂)₃₋₈—,    -   R^(14′″) is H, OH, C₁₋₇-alkyl, O—C₁₋₇-alkyl, phenyl, O-aryl,        CF₃, Cl or F, with the proviso that the two radicals R^(14′″)        are identical or different,    -   in the form of their possible stereoisomers as racemates or        diastereomerically pure enantiomers or in the form of mixtures        of enantiomers, in which the respective enantiomers are present        in nonequimolar amounts.

Preferred are salt-forming compounds of dimethyl-(3-arylbut-3-enyl)aminecompounds of the general formula IV, in which

-   -   R^(1′″) is C₁₋₃-alkyl and R^(2′″) is H or C₁₋₃-alkyl, or R^(1′″)        and    -   R^(2′″) together are —(CH₂)₂₋₄— or —(CH₂)₂—CHR^(7′″),    -   R^(3′″) is H or C₁₋₃-alkyl,    -   R^(4′″) is H, OH, CF₃, Cl, F or OR^(8′″),    -   R^(5′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl, CHF₂, CF₃,        Cl, F or OR^(8′″), and    -   R^(6′″) is H, OH, O—C₁₋₄-alkyl, O-benzyl, CF₃, Cl, F or        OR^(8′″),    -   with the proviso that two of the radicals R^(4′″), R^(5′″) or        R^(6′″) are H, or    -   R^(4′″) and R^(5′″) together are —CH═C(R^(9′″))—O— or        —CH═C(R^(9′″))—S—, with the proviso that R^(6′″) is H, or    -   R^(5′″) and R^(6′″) together are —CH═CH—C(OR^(10′″))═CH—, with        the proviso that R^(4′″) is H, and    -   R^(7′″) is C₁₋₄-alkyl, CF₃, Cl or F.

Particularly preferred are salt-forming compounds ofdimethyl-(3-arylbut-3-enyl)amine compounds of the general formula IV, inwhich R^(1′″) is CH₃ or C₃H₇ and R^(2′″) is H, CH₃ or CH₂CH₃, or R^(1′″)and R^(2′″) together are —(CH₂)₂₋₃— or —(CH₂)₂—CHR^(7′″),

-   -   R^(3′″) is H, CH₃ or CH₂CH₃,    -   R^(4′″) is H or OH, R^(5′″) is H, OH, OCH₃, CHF₂ or OR_(8′″) and        R^(6′″) is H, OH or CF₃, with the proviso that two of the        radicals R^(4′″), R^(5′″) or R^(6′″) are H, or    -   R^(4′″) and R^(5′″) together are —CH═C(CH₃)—S—, with the proviso        that R^(6′″) is H, or    -   R^(5′″) and R^(6′″) together are —CH═CH—C(OH)═CH—, with the        proviso that R^(4′″) is H, and    -   R^(8′″) is CO—C₆H₄—R^(11′″) where R^(11′″) is OC(O)—C₁₋₃-alkyl        in the ortho-position.

Very particularly preferred are salt-forming compounds ofdimethyl-(3-arylbut-3-enyl)amine compounds of the general formula IV, inwhich

-   -   R^(1′″) is CH₃ and R^(2′″) is H or CH₃ or R^(1′″) and R^(2′″)        together are —(CH₂)₂₋₃— or —(CH₂)₂—CH(CH₃)—,    -   R^(3′″) is H or CH₃,    -   R^(4′″) is H, R^(5′″) is OH or OR^(8′″), R^(6′″) is H, and        R^(8′″) is CO—C₆H₄—R^(11′″) where R^(11′″) is OC(O)—CH₃ in the        ortho-position.

Most preferred is the salt-forming compound ofdimethyl-(3-arylbut-3-enyl)amine compounds of the general formula IVtrans-(−)-(1R)-3-[1-(2-dimethylamino-1-methylethyl)propenyl]phenol.

The preparation of the salt-forming compounds ofdimethyl-(3-arylbut-3-enyl)amine compounds of the general formula IVand, if appropriate, the separation into the optically pure antipodescan be carried out according to customary methods known to the personskilled in the art. Preferably, the preparation and, if appropriate, theseparation of these compounds are carried out as described in EP 0 799819 A1. The corresponding literature description is hereby inserted asreference and is thus regarded as part of the disclosure.

As salt-forming antiobesity agents, the pharmaceutical salt according tothe invention can preferably contain D-norpseudoephedrine,phenylpropanolamine, amfepramone, mefenorex or ephedrine.

As salt-forming analeptics and/or antihypoxemics, the pharmaceuticalsalt according to the invention can preferably contain norfenefrine,heptaminol or amezinium, particularly preferably amezinium.

As salt-forming opioid antagonists, the pharmaceutical salt according tothe invention can preferably contain levallorphan, naloxone ornaltrexone.

As a salt-forming anthelmintic, the pharmaceutical salt according to theinvention can preferably contain pyrvinium.

As salt-forming antiallergics, the pharmaceutical salt according to theinvention can preferably contain reproterol, triprolidine, hydroxyzine,azelastine, diphenhydramine, promethazine, pheniramine,dexchlorpheniramine, clemastine, tramazoline, brompheniramine,dimetindene, levocabastine, doxylamine, cyproheptadine, carbinoxamine,meclozine, bamipine, chlorphenoxamine, ketotifen or cetirizine,particularly preferably diphenhydramine.

As salt-forming antiarrhythmics, the pharmaceutical salt according tothe invention can preferably contain orciprenaline, aprindine,verapamil, metoprolol, quinidine, amiodarone, sotalol, propafenone,diltiazem, disopyramide, propranolol, ipatropium [sic], mexiletine,prajmaline, procainamide, gallopamil, propafenone, detajmium,flecainide, oxprenolol or tocainide, particularly preferably verapamilor diltiazem.

As salt-forming antibiotics, the pharmaceutical salt according to theinvention can preferably contain vancomycin, tetracycline, clindamycin,minocycline, lincomycin, bacampicillin, amicacin, chlortetracycline,neomycin, tobramycin, netilmicin, quinine, chloroquine ciprofloxacin,clindamycin, colistine, erythromycin, gentamicin, tobramycin [sic],cefetametpivotil, amantadine, halofantrine, saquinavir, mefloquine,framycetin, cefepime, bromhexine, cefpodoximeproxetil, oxytetracycline,proguanil, pefloxacine, polymyxin B, hydroxychloroquine, spectinomycin,sultamicillin, valaciclovir or grepafloxacin.

As salt-forming antidementive (nootropics), the pharmaceutical saltaccording to the invention can preferably contain butalamine, memantine,pyritinol, donepezil, moxaverine, meclofenoxate, dihydroergotoxin,viquidil, naftidrofuryl, dihydroergocornine, dihydroergocristine,benzyclan, procaine, deamol, diisopropylamine or 3-pyridylmethanol.

As a salt-forming antidiabetic, the pharmaceutical salt according to theinvention can preferably contain metformin.

As salt-forming antiemetics and/or antivertiginous agents, thepharmaceutical salt according to the invention can preferably containbetahistidine, dolasetrone, meclozine, hydroxycine, diphenhydramine,pyridoxine, granisetrone, triflupromazine, triethyl-perazine,betahistine, alizapride or odansetrone, particularly preferablydiphenhydramine.

As a salt-forming antiepileptic, the pharmaceutical salt according tothe invention can preferably contain tiagabine.

As salt-forming antihypertensives, the pharmaceutical salt according tothe invention can preferably contain dihydralazine, prazosine,amiloride, bunazosine, nicardipine, alprenolol, candesartancilexetil,metoprolol, verapamil, propranolol, penbutolol, doxazosine, clonidine,benazepril, phenoxybenzamine, diltiazem, diisopropylamine, urapide,carteololl guanethidine, guanfacine, terazosine, oxprenolol,cicletanine, betaxolol, nebivolol, acebutolol, enalapril or indoramine,particularly preferably verapamil or diltiazem.

As salt-forming antihypotensives, the pharmaceutical salt according tothe invention can preferably contain etilefrine, pholedrine,norfenefrine, cafedrine, theodrenaline, oxilofrine, dobutamine,dopamine, phenylephrine, midodrine, heptaminol, oxedrine tartrate,pholedrine or gepefrine, particularly preferably phenylephrine.

As salt-forming antimycotics, the pharmaceutical salt according to theinvention can preferably contain benzalkonium, econazole, miconazole,methylrosanilinium, terbinafine, amorolfine, fenticonazole, dequalinium,oxyconazole, croconazole, isoconazole or sertaconazole.

As a salt-forming antiinflammatory, the pharmaceutical salt according tothe invention can preferably contain orphenadrine.

As salt-forming antitussives and/or expectorants, the pharmaceuticalsalt according to the invention can preferably contain ambroxole,doxycycline, bromhexine, dextromethorphan, diphenhydramine, terbutaline,chlorphenamine, eprazinone, ephedrine, chlorbutinol, pentoxyverine,pipazetate or benproperine, particularly preferably diphenhydramine.

As a salt-forming antisclerosis agent, the pharmaceutical salt accordingto the invention can preferably contain butalamine.

As β-receptor blockers and/or calcium channel blocker the pharmaceuticalsalt according to the invention can preferably contain acebutolol,nicardipine, alprenolol, metoprolol, verapamil, enalapril, bupranolol,penbutolol, propranolol, bisoprolol, esmolol, celiprolol, benazepril,diltiazem, mepindolol, sotalol, carteolol, gallopamil or oxprenolol,particularly preferably verapamil or diltiazem.

As salt-forming broncholytics and/or antiasthmatics, the pharmaceuticalsalt according to the invention can preferably contain ketotifen,reproterol, orciprenaline, salbutamol, terbutaline, ephedrine,tulobuterol, ipatropium [sic], fenoterol, terbutaline [sic], formoterol,salbutamol [sic], oxytropium or pirbuterol.

As salt-forming cholinergics, the pharmaceutical salt according to theinvention can preferably contain pyridostigmine, betanechol orneostigmine.

As salt-forming diuretics, the pharmaceutical salt according to theinvention can preferably contain amiloride or oxprenolol.

As salt-forming, circulation-promoting agents, the pharmaceutical saltaccording to the invention can preferably contain butalamine,naftidrofuryl, buflomedil, moxaverine, bencyclan or meclofenoxate.

As a salt-forming weaning agent, the pharmaceutical salt according tothe invention can preferably contain naltrexone, methadone,buprenorphine.

As salt-forming geriatrics, the pharmaceutical salt according to theinvention can preferably contain procaine or deanolace.

As salt-forming hypnotics and/or sedatives, the pharmaceutical saltaccording to the invention can preferably contain promethazine, zolpidemtartrate, midazolam, melperone or flurazepam.

As a salt-forming immunomodulator, the pharmaceutical salt according tothe invention can preferably contain levamisole.

As salt-forming oral and/or pharyngeal therapeutics, the pharmaceuticalsalt according to the invention can preferably contain chlorhexidine orcetylpyridinium.

As a salt-forming coronary agent, the pharmaceutical salt according tothe invention can preferably contain oxyfedrine.

As a salt-forming hypolipidemic, the pharmaceutical salt according tothe invention can preferably contain colestipol.

As salt-forming local anesthetics and/or neural therapeutics, thepharmaceutical salt according to the invention can preferably containbupivacaine, lidocaine, mepivacaine, ropivacaine, procaine, articaine orprilocaine.

As salt-forming gastric and/or intestinal agents, the pharmaceuticalsalt according to the invention can preferably contain pizotifen,pirenzepine, roxatidine, ranitidine, butinoline, methanthelinium ormetoclopramide.

As salt-forming migraine agents, the pharmaceutical salt according tothe invention can preferably contain lisuride, methysergide,dihydroergotamine, ergotamine, sumatriptan, rizatriptan or naratriptan.

As salt-forming muscle relaxants, the pharmaceutical salt according tothe invention can preferably contain alcuronium, mivacuronium,atracurium, vecurmium, pancurmium, suxamethonium, tolperisone, pridinol,orphenadrine or tizamidine.

As a salt-forming anesthetic, the pharmaceutical salt according to theinvention can preferably contain ketamine or midazolam.

As a salt-forming neuropathy preparation, the pharmaceutical saltaccording to the invention can preferably contain thiamine.

As salt-forming ophthalmologicals and/or otologicals, the pharmaceuticalsalt according to the invention can preferably contain oxybuprocaine,proxymetacaine, kanamycin, tolazoline, tetryzoline, tramazoline,phenylephrine, xylomethazoli [sic], naphazoline, timolol, metipranolol,betaxolol, befunolol, levobunolol, brimonidine, clonidine, pilocarpine,dipivefrine, aceclidine, apraclonidine, neostigmine, dorzolamide,atropine, scopolamine, cyclopentolate or homatropine, particularlypreferably phenylephrine.

As salt-forming Parkinson agents, the pharmaceutical salt according tothe invention can preferably contain amantadine, biperidene, selegiline,bromocriptine, trihexyphenidyl, metrixene, benzaseride, lisuride,benzatropine, ropinirol, pergolide, bupidine, procyclidine, pramipexol,bomapine or tiapride.

As salt-forming psychopharmaceutical agents, the pharmaceutical saltaccording to the invention can preferably contain tranylcypromine,amitriptyline, doxepine, maprotiline, clomipramine, opipramol,imipramine, trimipramine, lofepramine, desipramine, dibenzepine,nortriptyline, mianserine, citalopram, fluvoxamine, fluoxetil,trazodone, paroxetin, nefazodone, sertralin, viloxacin, venlafaxine,promethazine, chlorprothixene, zuclopenthixol, pipamperone,fluphenazine, flupentixol, melperone, prothipendyl, thioridazine,levomepromazine, quetiapine, triflupromazine, perazine, fenetylline,methylphenidate, hydroxycine, buspirone, deanolace or memantine.

As salt-forming rhinologicals/sinusitis agents, the pharmaceutical saltaccording to the invention can preferably contain diphenylpyraline,xylometazoline, oxymetazoline, tramazoline, indanazoline, naphazoline ortetryzoline.

As salt-forming spasmolytics, the pharmaceutical salt according to theinvention can preferably contain atropine, phenamazide,butylscopolaminium, propiverine, mebeverine, pipenzolate, oxybutynine,flavoxate, trospium, denaverine or glycopyrronium.

As salt-forming platelet aggregation inhibitors, the pharmaceutical saltaccording to the invention can preferably contain tirofiban, ticlopidineor clopidogrel.

As a salt-forming tuberculosis agent, the pharmaceutical salt accordingto the invention can preferably contain ethambutol.

As salt-forming urologicals, the pharmaceutical salt according to theinvention can preferably contain choline, tolterodine, phenoxybenzamine,atropine, propiverine, distigmine, emepronium, tamsulosine, doxazosine,terazosine, alfuzosine, bamethane, yohimbine or sildenafil.

As salt-forming cytostatics, the pharmaceutical salt according to theinvention can preferably contain aclarubicin, nimustatin, doxorubicin,bleomycin, vinblastine, vincristine, daunorubicin, decarbazine,vindesine, epirubicin, gemcitabine, procarbazil, mitoxantrone,bedamustine, idarubicin, aclarubicin [sic], irinotecan, topotecan,toremifen or tamoxifen.

The pharmaceutical salts according to the invention can be preparedaccording to customary methods known to the person skilled in the art.Preferably, for the preparation of the pharmaceutical salts according tothe invention, at least one salt of the respective active compound andat least one salt of the respective sugar substitute are in each casedissolved separately from one another in an amount of a solvent orsolvent mixture which is as small as possible, optionally with warming.

Both solutions are then combined, optionally mixed and optionallycooled. If the pharmaceutical salt according to the invention of theactive compound and the sugar substitute precipitates at least partiallyfrom the optionally cooled solution, this is separated off according tocustomary methods, preferably by suction filtration. The pharmaceuticalsalt separated off is then purified, if necessary, according tocustomary methods known to the person skilled in the art, for example byrecrystallization, washing or by stirring in a suitable solvent.

If the pharmaceutical salt has still not completely precipitated, theremaining solution is preferably concentrated completely on a rotaryevaporator and the pharmaceutical salt according to the invention isextracted from the residue according to customary methods known to theperson skilled in the art and purified as described above.

The solvent or solvent mixture suitable in each case for the preparationand the suitable reaction conditions, such as, for example, temperatureor reaction time, can be determined by the person skilled in the artwith the aid of simple preliminary tests. If both the active compoundsalt and the salt of the sugar substitute have an adequate solubility inwater, the solvent used is preferably water. The salt of the respectiveactive compound employed is preferably its hydrochloride, hydrobromide,phosphate, hydrogenphosphate, hydrogensulfate, sulfate, nitrate ormetilsulfate. The salt of the respective sugar substitute employed ispreferably its sodium, potassium, calcium or ammonium salt.

Of course, it is also possible to react the respective active compoundper se with [sic] the free acid of a sugar substitute with one anotherin a suitable reaction medium and to isolate and, if appropriate, topurify the pharmaceutical salt thus obtained according to customarymethods known to the person skilled in the art.

A further subject of the present invention are medicaments comprising atleast one pharmaceutical salt according to the invention and, ifappropriate, physiologically tolerable excipients. The correspondingmedicaments can be used for the treatment of the indications known forthe respective active compounds.

Preferably, medicaments according to the invention which contain atleast one pharmaceutical salt according to the invention of asalt-forming opioid, opioid analog, ephedrine, chloroquine, lidocaine,ethaverine, preglumetacin or triflupromaazine or a salt-forming compoundof the general formula I, II, III or IV indicated above and a sugarsubstitute are employed for the control of pain. Preferably, themedicaments according to the invention contain the correspondingsaccharinates as pharmaceutical salts of these active compounds.

For the treatment of urinary incontinence, medicaments according to theinvention are preferably employed which contain at least onepharmaceutical salt of a salt-forming compound of the general formula I,II, III or IV indicated above, or a compound from the group consistingof oxybutymine, tolterodine, propiverine and trospium and a sugarsubstitute. Preferably, the medicaments according to the inventioncontain the corresponding saccharinates as pharmaceutical salts of theseactive compounds.

The medicaments according to the invention can be present in solid,semisolid or liquid form. Preferably, the medicaments according to theinvention are suitable for oral administration.

In a preferred embodiment, the medicament according to the invention ispresent formulated as a gel, chewing gum, juice, spray, tablet, chewabletablet, coated tablet, powder, if appropriate filled into capsules,easily reconstitutable dry preparations, preferably as a gel, as anaqueous or oily juice, as a sublingual spray, tablets or chewabletablets.

Likewise preferably, the medicament according to the invention can alsobe present formulated in multiparticulate form, preferably in the formof micro-tablets, microcapsules, granules, active compound crystals orpellets, particularly preferably in the form of microtablets, granulesor pellets, optionally filled into capsules or compressed to givetablets.

If the medicament according to the invention is present in the form ofgranules or pellets, these can preferably have a size in the range from0.1 to 3 mm, particularly preferably in the range from 0.5 to 2 mm.

If the medicament according to the invention is present in the form ofmicrotablets, these can preferably have a diameter in the range from 0.5to 5 mm, particularly preferably in the range from 1 to 3 mm and veryparticularly preferably in the range from 1 to 2 mm.

If the medicament according to the invention is present in the form ofactive compound crystals, microparticles, micropellets or microcapsules,these can preferably have a diameter in the range from 10 μm to 1 mm,particularly preferably in the range from 15 μm to 0.5 mm and veryparticularly preferably in the range from 30 μm to 200 μm.

Depending on embodiment, the medicaments according to the invention canmoreover contain the customary physiologically tolerable excipientsknown to the person skilled in the art as further constituents.

If the medicaments according to the invention are present in the form oftablets or microtablets, these can be present as physiologicallytolerable excipients, preferably microcrystalline cellulose, celluloseethers, lactose, starch, starch derivatives, sugar alcohols, calciumhydrogenphosphate and the customary binders, flow regulators, lubricantsand/or disintegrants known to the person skilled in the art.

If the medicaments according to the invention are present in the form ofgels or chewing gums, these can preferably contain methylparaben,propylparaben, xylitol and/or xanthan gum as physiologically tolerableexcipients.

If the medicaments according to the invention are present in the form ofpellets, granules or micropellets, these can preferably containmicrocrystalline cellulose, cellulose ethers, lactose, starch and starchderivatives, sugar alcohols, calcium hydrogenphosphate, fatty alcohols,esters of glycerol or fatty acid esters as physiologically tolerableexcipients.

If the medicaments according to the invention are present in the form ofmicrocapsules or microparticles, these can contain, depending on thenature of the process employed for their preparation, the customaryphysiologically tolerable excipients known to the person skilled in theart.

The medicaments according to the invention can be prepared by customarymethods known to the person skilled in the art.

If the medicaments according to the invention are present in the form oftablets, preferably the pharmaceutical salt according to the inventionand, if appropriate, the physiologically tolerable excipients arepreferably mixed homogeneously with one another, processed to givegranules by means of moist, dry or melt granulation and compressed togive tablets or produced by direct tableting of the pharmaceutical saltwith further excipients. In addition, the tablets can preferably beproduced by compression of optionally coated pellets, active compoundcrystals, microparticles or microcapsules.

The medicaments according to the invention in the form of pellets canpreferably be produced by mixing the pharmaceutical salt andphysiologically tolerable excipients, extrusion and spheronization, bybuild-up pelletization or by direct pelletization in a high-speed mixeror in the rotor fluidized bed. The pellets are particularly preferablyprepared by extrusion of moist masses and subsequent spheronization.

Microcapsules are prepared according to customary microencapsulationprocesses, such as, for example, by spray drying, spray solidificationor coacervation.

The medicaments according to the invention in semisolid form, such as,for example, gels or chewing guns, are preferably suitable for theadministration of the pharmaceutical salt according to the invention viathe oral mucosa, the medicaments according to the invention in solid orliquid form, such as, for example, oily or aqueous juices, tablets ormultiparticulate forms are preferably suitable for the administration ofthe pharmaceutical salt according to the invention via the gastrictract. If the absorption of active compound from the medicamentaccording to the invention in solid form is only intended via thegastric tract, they must have at least one enteric coating. This entericcoating enables them to pass through the gastric tract undissolved andthe pharmaceutical salt is only released in the intestinal tract.Preferably, the enteric coating dissolves at a pH of between 5 and 7.5.

The medicament according to the invention can contain the pharmaceuticalsalt according to the invention also partially or completely indelayed-release form.

The delaying of the release of active compound is preferably based onthe application of a release-delaying coating, on embedding in arelease-delaying matrix, binding to an ion-exchange resin or on acombination of these abovementioned release-delaying methods.

Preferably, the release-delaying coating is based on a water-insoluble,optionally modified natural or synthetic polymer or on a natural,semisynthetic or synthetic wax or fat or fatty alcohol or a mixture ofat least two of these abovementioned components.

Water-insoluble polymers employed for the preparation of arelease-delaying coating are preferably poly-(meth)acrylates,particularly preferably poly(C₁₋₄) alkyl (meth)acrylates,poly(C₁₋₄)dialkylamino-(C₁₋₄)-alkyl (meth)acrylates and/or theircopolymers, very particularly preferably ethyl acrylate/methylmethacrylate copolymers having a molar ratio of the monomers of 2:1,ethyl acrylate/methyl methacrylate/trimethylammonium ethyl methacrylatechloride copolymers having a molar ratio of the monomers of 1:2:0.1,ethyl acrylate/methyl methacrylate/trimethylammonium ethyl methacrylatechloride copolymers having a molar ratio of the monomers of 1:2:0.2 or amixture of at least two of these abovementioned polymers as a coatingmaterial.

These coating materials are obtainable on the market as 30% strength byweight aqueous latex dispersions under the names Eudragit RS30D®,Eudragit NE30D® and Eudragit RL30D® and are preferably also employed asa coating material as such.

Likewise preferably, the water-insoluble polymers employed for thepreparation of the release-delaying coating for the medicamentsaccording to the invention can be polyvinyl acetates, optionally incombination with further excipients. These are obtainable on the marketas an aqueous dispersion containing 27% by weight of polyvinyl acetate,2.5% by weight of povidone and 0.3% by weight of sodium lauryl sulphate(Kollicoat SR 30 D®).

In a further preferred embodiment, the release-delaying coatings of themedicaments according to the invention are based on water-insolublecellulose derivatives, preferably alkylcelluloses, such as, for example,ethylcellulose, or on cellulose esters, such as, for example, celluloseacetate, as a coating material. The coatings of ethylcellulose orcellulose acetate are preferably applied from aqueous pseudolatexdispersion.

Aqueous ethylcellulose-pseudolatex dispersions are stocked on the marketas 30% strength by weight dispersions (Aquacoat®) or as 25% strength byweight dispersions (Surelease®) and as such are preferably also employedas a coating material.

As natural, semisynthetic or synthetic waxes, fats or fatty alcohols,the release-delaying coating in the medicament according to theinvention can preferably contain carnauba wax, beeswax, glycerolmonostearate, glycerol monobehenate (Compritol ATO888®), glycerolditripalmitostearate (Precirol AT05®), microcrystalline wax, cetylalcohol, cetylstearyl alcohol, or a mixture of at least two of thesecomponents.

If the release-delaying coating is based on a water-insoluble,optionally modified natural and/or synthetic polymer, the coatingdispersion or solution can contain, in addition to the correspondingpolymer, a customary physiologically tolerable plasticizer known to theperson skilled in the art in order to lower the minimum film temperaturenecessary.

Suitable plasticizers are, for example, lipophilic diesters of analiphatic or aromatic dicarboxylic acid of C₆-C₄₀ and an aliphaticalcohol of C₁-C₈, such as, for example, dibutyl phthalate, diethylphthalate, dibutyl sebacate or diethyl sebacate, hydrophilic orlipophilic esters of citric acid, such as, for example, triethylcitrate, tributyl citrate, acetyltributyl citrate or acetyltriethylcitrate, polyalkylene glycols, such as, for example, polyethyleneglycols or propylene glycols, esters of glycerol, such as, for example,triacetin, Myvacet® (acetylated mono- and diglycerides, C₂₃H₄₄O₅ toC₂₅H₄₇O₇), medium-chain triglycerides (Miglyol®), oleic acid or mixturesof at least two of the abovementioned plasticizers.

Preferably, aqueous dispersions of Eudragit RS® and optionally EudragitRL® contain triethyl citrate as a plasticizer.

Preferably, the release-delaying coating contains the plasticizer(s) inamounts of 5 to 50% by weight, particularly preferably 10 to 40% byweight and very particularly preferably 10 to 30% by weight, based onthe amount of the polymer employed.

In individual cases, for example for cellulose acetate, higher amountsof plasticizers, preferably up to 110% by weight, based on the amount ofcellulose acetate, can also be employed.

In addition, the release-delaying coating can contain further customaryexcipients known to the person skilled in the art, such as, for example,lubricants, preferably talc or glycerol monostearate, color pigments,preferably iron oxides or titanium dioxide, or surfactants, such as, forexample, Tween 80®.

The release profile of the delayed active compound component can beadjusted by the customary methods known to the person skilled in theart, such as, for example, by the thickness of the coating or by the useof further excipients as constituents of the coating. Suitableexcipients are, for example, hydrophilic or pH-dependent pore-formingagents, such as, for example, sodium carboxymethylcellulose, celluloseacetate phthalate, hydroxypropylmethylcellulose acetate succinate,lactose, polyethylene glycol or mannitol or water-soluble polymers, suchas, for example, polyvinylpyrrolidone or water-soluble celluloses,preferably hydroxypropylmethylcellulose or hydroxypropylcellulose.

The release-delaying coating can also contain insoluble or lipophilicexcipients, such as, for example, alkylized silicone, which is stockedon the market, for example, as Aerosil R972®, or magnesium stearate forthe further intensification of the delaying.

The respective formulation of the medicament according to the inventioncan optionally also contain, in addition to the release-delayingcoating, at least one further coating. This can be, for example, acoating for improving the taste or an enteric coating.

The enteric coating is preferably based on methacrylic acid/methylmethacrylate copolymers having a molar ratio of the respective monomersof 1:1 (Eudragit L®), methacrylic acid/methyl methacrylate copolymershaving a molar ratio of the respective monomers of 1:2 (Eudragit S®),methacrylic acid/ethyl acrylate copolymers having a molar ratio of therespective monomers of 1:1 (Eudragit L30D-55®), methacrylic acid/methylacrylate/methyl methacrylate copolymers having a molar ratio of therespective monomers of 7:3:1 (Eudragit FS®), shellachydroxy-propylmethylcellulose acetate succinate, cellulose acetatephthalate or a mixture of at least two of these abovementionedcomponents, which can optionally also be employed in combination withthe abovementioned water-insoluble poly(meth)acrylates, preferably incombination with Eudragit NE30D® and/or Eudragit RL® and/or EudragitRS®.

The coatings can be applied by customary processes suitable for therespective coating and known to the person skilled in the art, such as,for example, by spraying on solutions, dispersions or suspensions, bymelt processes or by powder application processes. The solutions,dispersions or suspensions can be employed in the form of aqueous and/ororganic solutions or dispersions. In this context, aqueous dispersionsare preferably employed. Organic solvents which can preferably be usedare alcohols, for example ethanol or isopropanol, ketones, such as, forexample, acetone, esters, for example ethyl acetate, chlorinatedhydrocarbons, such as, for example, dichloromethane, with alcohols orketones being particularly preferably employed. It is also possible toemploy mixtures of at least two of the abovementioned solvents.

If the medicament is present in multiparticulate form and the activecompound is to be released at least partially in delayed form, therelease-delaying coating is preferably applied such that themultiparticulate forms comprising the active compound salt are coatedafter their preparation with the corresponding polymers and, ifappropriate, another active compound and/or the same active compoundsalt and, if appropriate, further physiologically tolerable excipientsfrom aqueous and/or organic media, preferably from aqueous media, withthe aid of the fluidized bed process and the coating is preferablysimultaneously dried in the fluidized bed at customary temperatures and,if appropriate, annealed if necessary.

Preferably, the drying of the coating is carried out forpoly(meth)acrylate coatings at a feed air temperature in the range from30 to 50°, particularly preferably in the range from 35 to 45° C.

For coatings based on cellulose, such as, for example, ethylcellulose orcellulose acetate, the drying is preferably carried out at a temperaturein the range from 50 to 80° C., particularly preferably in the rangefrom 55 to 65° C.

Wax coatings can be applied by melt coating in the fluidized bed andcooled at temperatures below the respective melt range after the coatingfor complete solidification. The application of wax coatings can also becarried out by spraying on their solutions in organic solvents.

For the modification of the active compound release profile, themedicament according to the invention can contain the pharmaceuticalsalt whose release is to be delayed also in a release-delaying matrix,preferably uniformly dispersed.

Matrix materials which can be used are physiologically tolerable,hydrophilic materials which are known to the person skilled in the art.Preferably, the hydrophilic matrix materials used are polymers,particularly preferably cellulose ethers, cellulose esters and/oracrylic resins. Very particularly preferably, the matrix materialsemployed are ethylcellulose, hydroxypropylmethylcellulose,hydroxypropylcellulose, hydroxymethylcellulose, poly(meth)acrylic acidand/or their derivatives, such as, for example, their salts, amides oresters.

Likewise preferred are matrix materials made of hydrophobic materials,such as hydrophobic polymers, waxes, fats, long-chain fatty acids, fattyalcohols or appropriate esters or ethers or mixtures of at least two ofthe abovementioned materials. Particularly preferably, the hydrophobicmaterials employed are mono- or diglycerides of C₁₂-C₃₀-fatty acidsand/or C₁₂-C₃₀-fatty alcohols and/or waxes or mixtures of at least twoof the abovementioned materials.

It is also possible to employ mixtures of the above-mentionedhydrophilic and hydrophobic materials as a release-delaying matrixmaterial.

The release-delaying matrix can be prepared by the customary methodsknown to the person skilled in the art.

A further subject of the invention is also the use of at least onepharmaceutical salt according to the invention and, if appropriate,physiologically tolerable excipients for the production of a medicament.The corresponding medicaments can be used for the treatment of theindications known for the respective active compounds.

Preferred is the use of at least one pharmaceutical salt of asalt-forming opioid, opioid analog, ephedrine, chloroquine, lidocaine,ethaverine, preglumetacin, truflupromazine or a salt-forming compound ofthe general formula I, II, III or IV indicated above for the productionof a medicament for the control of pain, the salts of these activecompounds used preferably being their saccharinates.

Likewise preferred is the use of at least one pharmaceutical salt of asalt-forming compound of the general formula I, II, III or IV indicatedabove for the production of a medicament for the treatment of urinaryincontinence, the salts of these active compounds used preferably beingtheir saccharinates.

The total amount of the respective pharmaceutical salt to beadministered to the patient varies, for example, depending on the theweight of the patient, on the indication and the degree of severity ofthe pain or of the disorder. It is known to the person skilled in theart on account of the properties of the respective active compounds inwhat doses these are to be administered in order to achieve the desiredeffect.

The pharmaceutical salts according to the invention of a pharmaceuticalactive compound and a sugar substitute are distinguished compared withthe conventionally used salts of these active compounds customarily by alower solubility in water. Preferably, these are the saccharinates ofthe respective active compounds, whose water solubility is usually ≦250mg/ml and, compared with the water solubility of the conventional saltsof the corresponding active compound, is usually lowered by at least50%.

By this means, the formulation of these pharmaceutical salts to givemedicaments, for example the preparation of granules by extrusion, isalso simplified. On account of the altered solubility, thepharmaceutical salts according to the invention further enable moreeffective release-delaying of the active compound using customarydelaying processes in comparison to salts customarily used.Delayed-release medicaments which contain these pharmaceutical saltsaccording to the invention can therefore be produced more simply andmore inexpensively. This also applies for other modifications of themedicaments according to the invention, such as, for example, withenteric coatings.

From the medicaments according to the invention, which are employed forthe administration of the respective pharmaceutical salt via the oralmucosa or the gastric tract, a largely controlled release of therespective active compound without the use of a release-delaying matrixand/or a release-delaying coating, but if appropriate with an entericcoating, is moreover achieved.

The medicaments according to the invention in the form to beadministered orally, which release the respective active compound asearly as on or immediately after administration, furthermore have theadvantage that their strongly bitter or nauseating taste is compensatedby the simultaneous release of the sugar substitute. The adherence tothe dosage instructions in the patients thereby improves and themedicaments which contain the respective active compound as a saltexperience a greater acceptance. The medicaments according to theinvention are moreover also suitable for diabetics.

For a large number of the abovementioned active compounds, the watersolubility of the conventional active compound salts is known, forexample from Pharmazeutische Stoffliste [Pharmaceutical Substance List],12th edition ABDATA Pharma-Daten-Service, 65735 Eschborn/Taunus. Thecorresponding disclosure [sic] is hereby inserted as reference and isthus regarded as part of the disclosure.

If the water solubility of an active compound salt is not known, it canbe determined according to the method indicated below, according towhich the water solubility of the pharmaceutical salts according to theinvention has also been determined:

In a clear colorless vessel made of transparent material, such as, forexample, glass or plastic, 1 ml of ion-free water or a fraction (amountA in ml) thereof is introduced at a temperature of 20° C. While stirringwith a magnetic stirrer rod, the conventional active compound salt to betested or the pharmaceutical salt according to the invention was thenadded in portions.

If the amount of salt B added (in mg) completely dissolved, furtheramounts of the respective salt were slowly added. Each further additionwas recorded and the solution behavior observed. As soon as the firstturbidity due to undissolved salt was found by observation against asuitable background, stirring was continued for a further 10 minutes. Ifundissolved constituents subsequently remained, the sum C (in mg) of theamount of substance employed was determined. If a clear solutionresulted again on stirring, further small amounts of the respective saltwere added and the mixture was in each case stirred again for 10 minutesuntil a first turbidity remained on account of undissolved salts. Theexcess amount of undissolved substance was then brought into solutionwith stirring by addition of small amounts of water. After a clearsolution had been obtained, the sum D (in ml) of the amount of wateremployed was determined. The solubility of the respective salt per 1 mlof water was then calculated according to the following formula:${{Water}\quad{solubility}\quad{of}\quad{the}\quad{active}\quad{compound}\quad{salt}\quad{in}\quad{mg}\text{/}{ml}\quad{of}\quad{water}} = \frac{\left( {C/A} \right) + \left( {C/D} \right)}{2}$

If the amount B added (in mg) of the respective salt did not dissolveimmediately and a turbidity resulted, after the addition of the salt themixture was stirred for a further 10 minutes. If undissolved salt stillremained then, the undissolved portion was brought into solution byaddition of small amounts of water with stirring. After obtainment of aclear solution, the sum E (in ml) of the amounts of water employed wasdetermined. The solubility of the respective salt per 1 ml of water wasthen calculated according to the following formula:${{Water}\quad{solubility}\quad{of}\quad{the}\quad{active}\quad{compound}\quad{salt}\quad{in}\quad{mg}\text{/}{ml}\quad{of}\quad{water}} = \frac{B}{E}$

The invention is explained below with the aid of examples. Theseexplanations are only by way of example and do not restrict the generalinventive concept.

EXAMPLES Example 1

The preparation and the subsequent separation of the optically purecompound (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenolwas carried out according to DE-A-4426245. The corresponding part of thedisclosure [sic] is hereby inserted as reference and is thus regarded aspart of the disclosure.

For the preparation of(+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenolsaccharinate, 2.58 g (10 mmol) of(+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenolhydrochloride and 2.42 g (10 mmol) of saccharin-sodium dihydrate were ineach case completely dissolved with warming in an amount of water whichwas as small as possible. Both solutions were then mixed with oneanother with stirring and then placed in a cool place overnight. Theprecipitated(+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenolsaccharinate was separated off from the supernatant mother liquor,purified with ethanol and isolated according to conventional methods.

Example 2

For the preparation of diphenhydramine saccharinate, 5.0 g (17.1 mmol)of diphenhydramine hydrochloride and 4.13 g (17.1 mmol) ofsaccharin-sodium dihydrate were in each case completely dissolved withwarming in an amount of water which was as small as possible. Bothsolutions were then mixed with one another with stirring and then placedin a cool place overnight. The precipitated diphenhydramine saccharinatewas separated off from the supernatant mother liquor, purified withethanol and isolated according to conventional methods.

Example 3

For the preparation of verapamil saccharinate, 415 mg (0.845 mmol) ofverapamil hydrochloride and 204 mg (0.845 mmol) of saccharin-sodiumdihydrate were in each case completely dissolved with warming in anamount of water which was as small as possible. Both solutions were thenmixed with one another with stirring and then placed in a cool placeovernight. The precipitated verapamil saccharinate was separated offfrom the supernatant mother liquor, purified with ethanol and isolatedaccording to conventional methods.

Example 4

For the preparation of morphine saccharinate, 285 mg (0.76 mmol) ofmorphine hydrochloride trihydrate and 183 mg (0.76 mmol) ofsaccharin-sodium dihydrate were in each case completely dissolved withwarming in an amount of water which was as small as possible. Bothsolutions were then mixed with one another with stirring and then placedin a cool place overnight. The precipitated morphine saccharinate wasseparated off from the supernatant mother liquor, purified with ethanoland isolated according to conventional methods.

Example 5

For the preparation of an oral gel, 0.33 g of methylparaben, 0.05 g ofpropylparaben and 75.0 g of xylitol were first dissolved in 198.0 g ofpurified water at a temperature of 80° C. and the mixture was thencooled to 40° C. Then, initially 0.94 g of diphenhydramine saccharinateobtained according to example 2 and subsequently 2 g of xanthan gum wereadded with stirring, stirring was continued for one hour and evaporatedwater was replaced. After cooling to a temperature of 20 to 25° C., themixture was flavored with 0.625 g of Tutti-Frutti 9/008897 (DragocoGerberding & Co. AG, 37603 Holzminden) while stirring.

Example 6

5 g of comminuted chewing gum mass (Popeye Amural Confections,Yorkville, Ill., USA) were warmed to a temperature of 30 to 40° C. in aFanta dish. 187.9 mg of diphenhydramine saccharinate obtained accordingto example 2 were then incorporated into the viscous chewing gum massusing a pestle. The homogeneous mass was then portioned into teflonizedmolds to give portions of 1 g each.

The taste test showed that the chewing gums which contained thediphenhydramine saccharinate had an excellent taste at the start andwere still enjoyable even after a relatively long chewing time.

Example 7

For the preparation of a juice on an aqueous basis, 0.33 g ofmethylparaben, 0.05 g of propylparaben and 75.0 g of xylitol weredissolved in 199.22 g of purified water at a temperature of 80° C. Themixture was cooled to 40° C. and 78.5 mg of(+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenolsaccharinate obtained according to example 1 were added with stirring.0.25 g of xanthan gum was then added, stirring was continued for onehour and evaporated water was replaced. After cooling to [lacuna]temperature of 20 to 25° C., the mixture was flavored while stirringwith 0.075 g of orange-mandarin flavor 10888-56 (Givaudan Roure FlavorsLtd. CH 8600 Dübendorf).

Example 8

In this example, the water solubility of certain pharmaceutical saltsand of conventional salts of the corresponding active compound wasdetermined according to the method indicated above. The solubilityvalues thus obtained are presented in table 1 below: TABLE 1 Comparisonof the water solubilities of certain pharmaceutical salts according tothe invention and corresponding conventional salts of these activecompounds. The conventional salt employed in each case is indicated inbrackets. Solubility of Solubility of the active the active compoundcompound salt saccharinate in mg/ml of in mg/ml of Active compound waterwater (−)-(1R,2R)-3-(3- 261 31 dimethylamino-1-ethyl- (hydrochloride)2-methylpropyl)phenol (1RS,3RS,6RS)-6- 500 71 dimethylaminomethyl-1-(hydrochloride) (3-methoxy- phenyl)cyclohexane- 1,3-diol [sic](+)-(1S,2S)-3-(3- 650 55 dimethylamino-1-ethyl- (hydrochloride)2-methylpropyl)phenol (−)-(1S,2S)-3-(3- 568 130 dimethylamino-1-ethyl-(hydrochloride) 1-fluoro-2-methyl- propyl)phenol (−)-(2S,3S)-1- 2000  90dimethylamino-3-(3- (hydrochloride) methoxyphenyl)- 2-methylpentan-3-ol(+)-(1R,2R,4S)-2-  33 10 dimethylaminomethyl-4- (hydrochloride)(4-fluorobenzyl-oxy)- 1-(3-methoxy- phenyl)cyclohexanol Morphine  52 25(hydrochloride trihydrate) Amezinium  25 8 (metilsulfate) Phenylephrine1250  380 (hydrochloride) Verapamil 200 7 (hydrochloride)Diphenhydramine 1000  7 (hydrochloride) Benzalkonium 500 <2(hydrochloride) Codeine 250 200 (phosphate hemihydrate) Hydromorphone330 130 (hydrochloride) Buprenorphine  14 2 (hydrochloride)

As can be seen from the solubility values according to table 1, thesolubility of the respective active compound saccharinates is loweredcompared with the corresponding conventional active compound salts.

1. A pharmaceutical salt of a pharmaceutical active compound and atleast one sugar substitute with the exception of the respectivepharmaceutical salt of a sugar substitute and tramadol, (+)-tramadol,(−)-tramadol, (+)-demethyltramadol and (−)-demethyltramadol.
 2. Thepharmaceutical salt as claimed in claim 1, characterized in that thesolubility of the salt in water is ≦250 mg/ml of water, preferably ≦200mg/ml, particularly preferably ≦150 mg/ml, very particularly preferably≦100 mg/ml.
 3. The pharmaceutical salt as claimed in claim 1,characterized in that the salt-forming sugar substitute is saccharin,cyclamate or acesulfam, preferably saccharin.
 4. The pharmaceutical saltas claimed in claim 1, characterized in that the salt-forming activecompound is selected from the group consisting of the salt-forminganalgesics, antiobesity agents, analeptics, antihypoxemics,antirheumatics, opioid antagonists, anthelmintics, antiallergics,antiarrhythmics, antibiotics, anti-dementives (nootropics),antidiabetics, anti-emetics, antivertiginous agents, antiepileptics,antihypertensives, antihypotensives, antimycotics, antiinflammatories,antitussives, expectorants, arteriosclerosis agents, β-receptorblockers, calcium channel blockers, broncholytics, anti-asthmatics,cholinergics, diuretics, circulation-promoting agents, weaning agents,geriatrics, hypnotics, sedatives, immunomodulators, oral therapeutics,pharyngeal therapeutics, coronary agents, hypolipidemics, localanesthetics, neural therapeutics, gastric agents, intestinal agents,migraine agents, muscle relaxants, anesthetics, neuropathy preparations,ophthalmologicals, otologicals, Parkinson agents, psychopharmaceuticals,rhinologicals, sinusitis agents, spasmolytics, platelet aggregationinhibitors, tuberculosis agents, urologicals and cytostatics.
 5. Thepharmaceutical salt as claimed in claim 4, characterized in that theactive compound is selected from the group consisting of thesalt-forming analgesics, analeptics, antihypoxemics, antiallergics,antiarrhythmics, antiemetics, antivertiginous agents, antihypertensives,antihypotensives, antitussives, expectorants, β-receptor blockers,calcium channel blockers, ophthalmologicals, otologicals, spasmolyticsand urologicals, preferably from the group consisting of thesalt-forming analgesics.
 6. The pharmaceutical salt as claimed in claim4, characterized in that the salt-forming analgesic is selected from thegroup consisting of the salt-forming opioids, the salt-forming opiodanalogs, ephdrine, chloroquine lidocaine, ethaverine, preglumetacin andtriflupromazine.
 7. The pharmaceutical salt as claimed in claim 6,characterized in that the salt-forming opioid or opioid analog isselected from the group consisting of morphine, codeine, ethylmorphine,diacetylmorphine, dihydrocodeine, etorphine, hydrocodone, hydromorphone,levorphanol, oxycodone, oxymorphone, pethidine, ketobemidone, fentanyl,alfentanil, remifentanil, sufentanil, levomethadone, levomethadyl,dextromoramide, dextropropoxyphene, diphenoxylate, piritramide,tilidine, buprenorphine, butorphanol, dezozine, nalbuphine, nalorphine,pentazocine, nefopam, flupirtin and meptazinol.
 8. The pharmaceuticalsalt as claimed in claim 7, characterized in that the salt-formingopioid is selected from the group consisting of morphine, codeine,hydrocodone, hydromorphone, oxycodone, tilidine, fentanyl andbuprenorphine.
 9. The pharmaceutical salt as claimed in claim 1,characterized in that the salt-forming active compound is a salt-formingcompound of 1-phenyl-3-dimethylaminopropane compounds of the generalformula I

in which X is OH, F, Cl, H or an OCOR⁶ group, R¹ is a C₁₋₄-alkyl group,R² is H or a C₁₋₄-alkyl group and R³ is H or a straight-chain C₁₋₄-alkylgroup or the radicals R² and R³ together form a C₄₋₇-cycloalkyl radical,and if R⁵ is H, R⁴ is meta-O-Z where Z is H, C₁₋₃-alkyl,PO(O—C₁₋₄-alkyl)₂, CO(OC₁₋₅-alkyl), CONH—C₆H₄—(C₁₋₃-alkyl), CO—C₆H₄—R⁷,where R⁷ is ortho-OCOC₁₋₃-alkyl or meta- or para-CH₂N(R⁸)₂ where R⁸ isC₁₋₄-alkyl or 4-morpholino, or R⁴ is meta-S—C₁₋₃-alkyl, meta-Cl, meta-F,meta-CR⁹R¹⁰R¹¹ where R⁹, R¹⁰, R¹¹ are H or F, ortho-OH,ortho-O—C₂₋₃-alkyl, para-F or para-CR⁹R¹⁰R¹¹ where R⁹, R¹⁰, R¹¹ are H orF, or if R⁵ is para-Cl, —F, —OH or —O—C₁₃-alkyl, R⁴ is meta-Cl, —F, —OHor —O—C₁₋₃-alkyl, or R⁴ and R⁵ together are 3,4-OCH═CH— or 3,4-OCH═CHO—,R⁶ is C₁₋₃-alkyl, in the form of their possible stereoisomers asracemates or diastereomerically pure enantiomers or in the form ofmixtures of enantiomers, in which the respective enantiomers are presentin nonequimolar amounts.
 10. The pharmaceutical salt as claimed in claim9, characterized in that X is OH, F, Cl or H, R¹ is a C₁₋₄-alkyl group,R² is H or CH₃ and R³ is H or CH₃ and if R⁵ is H, R⁴ ismeta-O—C₁₋₃-alkyl, meta-OH, meta-S—C₁₋₃-alkyl, meta-F, meta-Cl,meta-CH₃, meta-CF₂H, meta-CF₃ or para-CF₃ or if R⁵ is a para-Cl or —F,R⁴ is meta-Cl or —F, or R⁴ and R⁵ together are 3,4-OCH═CH—.
 11. Thepharmaceutical salt as claimed in claim 9, characterized in that theradicals R² and R³ have different meanings and the compounds of thegeneral formula I as claimed in claim 9 are present in the form of theirdiastereomers having the configuration Ia


12. The pharmaceutical salt as claimed in claim 9, characterized in thatthe salt-forming 1-phenyl-3-dimethylaminopropane compound is selectedfrom the group consisting of(1RS,2RS)-3-(3-dimethylamino-1-hydroxy-1,2-dimethylpropyl)phenol,(−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol,(+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol,(2RS,3RS)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol,(−)-(1S,2S)-3-(3-dimethylamino-1-ethyl-1-fluoro-2-methylpropyl)phenol,(+)-(1R,2R)-3-(3-dimethylamino-1-hydroxy-1,2-dimethylpropyl)phenol,(+)-(2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol and(−)-(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol. 13.The pharmaceutical salt as claimed in claim 1, characterized in that thesalt-forming active compound is a salt-forming compound of6-dimethylaminomethyl-1-phenylcyclohexane compounds of the generalformula II,

in which R^(1′) is H, OH, Cl or F, R^(2′) and R^(3′) are identical ordifferent and are H, C₁₋₄-alkyl, benzyl, CF₃, OH, OCH₂—C₆H₅,O—C₁₋₄-alkyl, Cl or F with the proviso that at least one of the radicalsR^(2′) or R^(3′) is H, R⁴ is H, CH₃, PO(O—C₁₋₄-alkyl)₂,CO(O—C₁₋₅-alkyl), CO—NH—C₆H₄—C₁₋₃-alkyl, CO—C₆H₄—R⁵, CO—C₁₋₅-alkyl,CO—CHR^(6′)—NHR^(7′) or an unsubstituted or substituted pyridyl,thienyl, thiazoyl [sic] or phenyl group, R^(5′) is OC(O)C₁₋₃-alkyl inthe ortho-position or CH₂—N(R^(8′))₂ in the meta- or para-position,where R^(8′) is C₁₋₄-alkyl or both radicals R^(8′) together with N arethe 4-morpholino radical, and R^(6′) and R^(7′) are identical ordifferent and are H or C₁₋₆-alkyl, with the proviso that if bothradicals R^(2′) and R^(3′) are H, R^(4′) is not CH₃ if R^(1′) is H, OHor Cl or R^(4′) is not H if R^(1′) is OH, in the form of their possiblestereoisomers as racemates or diastereomerically pure enantiomers or inthe form of mixtures of enantiomers, in which the respective enantiomersare present in nonequimolar amounts.
 14. The pharmaceutical salt asclaimed in claim 13, characterized in that R^(1′) is H, OH or F.
 15. Thepharmaceutical salt as claimed in claim 13, characterized in that thecompounds of the general formula II have a configuration in which thephenyl ring and the dimethylaminomethyl group are in each case arrangedin an equatorial position to one another.
 16. The pharmaceutical salt asclaimed in claim 13, characterized in that the salt-forming6-dimethylaminomethyl-1-phenylcyclohexane compound is selected from thegroup consisting of(−)-(1R,2R)-3-(2-dimethylaminomethylcyclohexyl)phenol,(1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexane-1,3-dioland(1RS,3RS,6RS)-6-(dimethylaminomethyl)-1-(3-hydroxyphenyl)cyclohexane-1,3-diol.17. The pharmaceutical salt as claimed in claim 1, characterized in thatthe salt-forming active compound is a salt-forming compound of1-phenyl-2-dimethylaminomethylcyclohexan-1-ol compounds of the generalformula III,

in which in each case A is O or S, R^(1″) is H, C₁₋₆-alkyl,C₂₋₆-alkenyl, C₅₋₇-cycloalkyl or halogenated C₁₋₆-alkyl, the group

R^(2′″) is C₁₋₆-alkyl, C₂₋₆-alkenyl, C₅₋₇-cycloalkyl-methyl, substitutedor unsubstituted phenyl or substituted or unsubstituted benzyl, in theform of their possible stereoisomers as racemates or diastereomericallypure enantiomers or in the form of mixtures of enantiomers, in which therespective enantiomers are present in nonequimolar amounts.
 18. Thepharmaceutical salt as claimed in claim 17, characterized in that R^(1″)is H, C₁₋₄-alkyl, 2′-methyl-2′-propenyl, cyclopentyl or fluoroethyl,with the proviso that R^(1″) is C₁₋₄-alkyl if A is S, R^(2″) isC₁₋₄-alkyl, C₂₋₄-alkenyl, cyclopentylmethyl, phenyl, C₁₋₄-alkoxyphenyl,benzyl, C₁₋₄-alkylbenzyl, mono- or dihalogenated phenyl or mono- ordihalogenated benzyl.
 19. The pharmaceutical salt as claimed in claim17, characterized in that R^(1″) is H, methyl, ethyl, isopropyl,2′-methyl-2′-propenyl, cyclopentyl or fluoroethyl, with the proviso thatR^(1″) is methyl if A is S, R^(2″) is methyl, propyl, 2′-methylpropyl,allyl, 2′-methyl-2′-propenyl, cyclopentylmethyl, phenyl,3-methoxyphenyl, benzyl, 4-tert-butylbenzyl, 4-chlorobenzyl,4-fluorobenzyl or 3,4-dichlorobenzyl.
 20. The pharmaceutical salt asclaimed in claim 17, characterized in that the compounds of the generalformula III have a configuration in which the phenyl ring and thedimethylaminomethyl group are in each case arranged in an equatorialposition to one another.
 21. The pharmaceutical salt as claimed in claim17, characterized in that the salt-forming1-phenyl-2-dimethylaminomethylcyclohexan-1-ol compound of the generalformula III is selected from the group consisting of(+)-(1R,2R,4S)-2-(dimethylaminomethyl)-4-(4-fluorobenzyloxy)-1-(3-methoxyphenyl)cyclohexanol,(+)-(1R,2R,4S)-2-dimethylaminomethyl-4-(4-chloro-benzyloxy)-1-(3-methoxyphenyl)cyclohexanoland(+)-(1R,2R,4S)-3-[2-dimethylaminomethyl-4-(4-fluorobenzyloxy)-1-hydroxycyclohexyl]phenol.22. The pharmaceutical salt as claimed in claim 1, characterized in thatthe salt-forming active compound is a salt-formingdimethyl-(3-arylbut-3-enyl)amine compound of the general formula IV, inwhich [sic]

the radical R^(1′″) is C₁₋₅-alkyl and R^(2′″) is H or C₁-₅-alkyl orR^(1′″) and R^(2′″) together are —(CH₂)₂₋₄—, —(CH₂)₂—CHR^(7′″) or—CH₂—CHR^(7′″)—CH₂—, R^(3′″) is H or C₁₋₅-alkyl, R^(4′″) is H, OH,C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl, CF₃, O—CF₃, Cl, F or OR^(8′″),R^(5′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl, CHF₂, CF₃, O—CF₃,Cl, F or OR^(8′″) and R^(6′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl,O-benzyl, CF₃, O—CF₃, Cl, F or OR^(8′″), with the proviso that two ofthe radicals R^(4′″), R^(5′″) or R^(6′″) are H, or R^(4′″) and R^(5′″)together are —CH═C(R^(9′″))—O— or —CH═C(R^(9′″))—S—, with the provisothat R^(6′″) is H, or R^(5′″) and R^(6′″) together are—CH═CH—C(OR^(10′″))═CH—, with the proviso that R^(4′″) is H, R^(7′″) isC₁₋₈-alkyl, C₃₋₈-cycloalkyl, O—C₁₋₄-alkyl, O-benzyl, CF₃, Cl or F,R^(8′″) is CO—C₁₋₅-alkyl, PO(O—C₁₋₄-alkyl)₂, CO—C₆H₄—R^(11′″),CO(O—C₁₋₅-alkyl), CO—CHR^(12′″)—NHR^(13 ′″), CO—NH—C₆H₃—(R^(14′″))₂ oran unsubstituted or substituted pyridyl, thienyl, thiazoyl [sic] orphenyl group, R^(9′″) is H or C₁₋₄-alkyl, R^(10′″) is H or C₁₋₃-alkyl,R^(11′″) is OC(O)—C₁₋₃-alkyl in the ortho-position or CH₂—N—(R^(15′″))₂in the meta- or para-position, where R^(15′″) is C₁₋₄-alkyl or bothradicals R^(15′″) together with N form the 4-morpholino radical,R^(12′″) and R^(13′″) are identical or different and are H, C₁₋₆-alkylor C₃₋₈-cycloalkyl or R^(12′″) and R^(13′″) together are —(CH₂)₃₋₈—,R^(14′″) is H, OH, C₁₋₇-alkyl, O—C₁₋₇-alkyl, phenyl, O-aryl, CF₃, Cl orF, with the proviso that the two radicals R^(14′″) are identical ordifferent, in the form of their possible stereoisomers as racemates ordiastereomerically pure enantiomers or in the form of mixtures ofenantiomers, in which the respective enantiomers are present innonequimolar amounts.
 23. The pharmaceutical salt as claimed in claim22, characterized in that R^(1′″) is C₁₋₃-alkyl and R^(2′″) is H orC₁₋₃-alkyl, or R^(1′″) and R^(2′″) together are —(CH₂)₂₋₄— or—(CH₂)₂—CHR^(7′″), R^(3′″) is H or C₁₋₃-alkyl, R^(4′″) is H, OH, CF₃,Cl, F or OR^(8′″), R^(5′″) is H, OH, C₁₋₄-alkyl, O—C₁₋₄-alkyl, O-benzyl,CHF₂, CF₃, Cl, F or OR^(8′″) and R^(6′″) is H, OH, O—C₁₋₄-alkyl,O-benzyl, CF₃, Cl, F or OR^(8′″), with the proviso that two of theradicals R^(4′″), R^(5′″) or R^(6′″) are H, or R^(4′″) and R^(5′″)together are —CH═C(R^(9′″))—O— or —CH═C(R^(9′″))—S—, with the provisothat R^(6′″) is H, or R^(5′″) and R^(6′″) together are—CH═CH—C(OR¹⁰′″)═CH—, with the proviso that R^(4′) is H, and R^(7′″) isC₁₋₄-alkyl, CF₃, Cl or F.
 24. The pharmaceutical salt as claimed inclaim 22, characterized in that R^(1′″) is CH₃ or C₃H₇ and R^(2′″) is H,CH₃ or CH₂CH₃, or R^(1′″) and R^(2′″) together are —(CH₂)₂₋₃— or—(CH₂)₂—CHR^(7′″), R^(3′″) is H, CH₃ or CH₂CH₃, R^(4′″) is H or OH,R^(5′″) is H, OH, OCH₃, CHF₂ or OR^(8′″) and R^(6′″) is H, OH or CF₃,with the proviso that two of the radicals R^(4′″), R^(5′″) or R^(6′″)are H, or R^(4′″) and R^(5′″) together are —CH═C(CH₃)—S—, with theproviso that R^(6′″) is H, or R^(5′″) and R^(6′″) together are —CH⊚CH—C(OH)═CH—, with the proviso that R^(4′″) is H, and R^(8′″) isCO—C₆H₄—R^(11′″) where R^(11′″) is OC(O)—C₁₋₃-alkyl in theortho-position.
 25. The pharmaceutical salt as claimed in claim 22,characterized in that R^(1′″) is CH₃ and R^(2′″) is H or CH₃ or R^(1′″)and R^(2′″) together are —(CH₂)₂₋₃— or —(CH₂)₂—CH(CH₃)—, R^(3′″) is H orCH₃, R^(4′″) is H, R^(5′″) is OH or OR^(8′″), R^(6′″) is H, and R^(8′″)is CO—C₆H₄—R^(11′″) where R^(11′″) is OC(O)—CH₃ in the ortho-position.26. The pharmaceutical salt as claimed in claim 22, characterized inthat the salt-forming dimethyl-(3-arylbut-3-enyl)amine compound presentis trans-(−)-(1R)-3-[1-(2-dimethylamino-1-methylethyl)propenyl]phenol.27. A medicament comprising at least one pharmaceutical salt as claimedin claim 1 and, if appropriate, physiologically tolerable excipients.28. A medicament comprising at least one pharmaceutical salt as claimedin claim 6 for the control of pain.
 29. A medicament comprising at leastone pharmaceutical salt as claimed in claim 9 for the control of urinaryincontinence.
 30. The medicament as claimed in claim 27, characterizedin that it are [sic] present formulated in the form of gels, chewinggums, juices, sprays, tablets, chewable tablets, coated tablets,powders, if appropriate filled into capsules, easily reconstitutable drypreparations, preferably in the form of gels, aqueous or oily juices,sublingual sprays, tablets or chewable tablets.
 31. The medicament asclaimed in claim 27, characterized in that it is present formulated inmultiparticulate form, preferably in the form of microtablets,microcapsules, granules, active compound crystals or pellets,particularly preferably in the form of microtablets, granules orpellets, optionally filled into capsules or compressed to give tablets.32. The medicament as claimed in claim 27, characterized in that thesalt is present at least partially in delayed-release form.
 33. Themedicament as claimed in claim 32, characterized in that delaying of therelease is carried out by applying a release-delaying coating, embeddingin a release-delaying matrix, binding to an ion-exchange resin or by acombination of at least two of these methods.
 34. The medicament asclaimed in claim 33, characterized in that the release-delaying coatingis based on a water-insoluble, optionally modified natural or syntheticpolymer, optionally in combination with a customary plasticizer, or on anatural, semisynthetic or synthetic wax or fat or fatty alcohol or amixture of at least two of these components.
 35. The medicament asclaimed in claim 33, characterized in that the matrix is based on ahydrophilic matrix material, preferably hydrophilic polymers,particularly preferably on cellulose ethers, cellulose esters and/oracrylic resins, very particularly preferably on ethylcellulose,hydroxypropylmethylcellulose, hydroxypropylcellulose,hydroxymethylcellulose, poly(meth)acrylic acid and/or their their salts,amides and/or esters.
 36. The medicament as claimed in claim 33,characterized in that the matrix is based on a hydrophobic matrixmaterial, preferably hydrophobic polymers, waxes, fats, long-chain fattyacids, fatty alcohols or appropriate esters or ethers or their mixtures,particularly preferably on mono- or diglycerides of C₁₂-C₃₀ fatty acidsand/or C₁₂-C₃₀-fatty alcohols and/or waxes or their mixtures.
 37. Themedicament as claimed in claim 27, characterized in that it has aprotective coating, preferably an enteric protective coating.
 38. Theuse of at least one pharmaceutical salt as claimed in claim 6 for theproduction of a medicament for the control of pain.
 39. The use of atleast one pharmaceutical salt as claimed in claim 9 for the productionof a medicament for the treatment of urinary incontinence.